Hydrocodone therapy

ABSTRACT

A hydrocodone composition, a hydrocodone dosage form, and a method of administering hydrocodone are disclosed and indicated for hydrocodone therapy.

FIELD OF THE INVENTION

[0001] This invention pertains to a novel therapeutic compositioncomprising hydrocodone. The invention concerns also a novel dosage formcomprising hydrocodone. Additionally, the invention relates to a novelmethod of administering a dose of hydrocodone from a therapeuticcomposition, and to a novel method of administering a dose ofhydrocodone from a dosage form that in both administrations are forproducing antitussive and analgesic therapy.

BACKGROUND OF THE INVENTION

[0002] Hydrocodone is chemically4,5-epoxy-3-methoxy-17-methyl-morphinan-6-one. The synthesis ofhydrocodone and its pharmaceutically acceptable acid addition salts aredescribed in U.S. Pat. No. 2,71 5,629 issued to Pfister et al, and inthe Merck Index, 11th Edition, page 757, entry 4708 (1989). Hydrocodoneis a narcotic antitussive and analgesic. The mechanism of physiologicaland pharmacological actions of hydrocodone is believed that it actsdirectly by depressing the cough centers for its antitussive therapy. Atantitussive doses, hydrocodone exerts also analgesic effects.Hydrocodone exhibits a complex pattern of metabolism includingO-demethylation, N-dimethylation and 6-keto reduction to thecorresponding 6-β-hydroxy metabolites.

[0003] The prior art administers hydrocodone in conventional tablet andsyrup forms, which forms dose-dump hydrocodone thereby providing aconcentration of hydrocodone followed by an absence of hydrocodone. Thispharmaceodynamic variability with its fluctuation in hydrocodoneavailability to hydrocodone receptor sites produces uncertainty as it isunknown if a dose of hydrocodone is present for needed therapy. Theprior art is deficient in providing controlled hydrocodone therapy to apatient seeking such therapy. The pharmacological properties ofhydrocodone are known in The Pharmacological Basis of Therapy, by Gilmanand Rall, 8th Edition, pg. 497, (1990); and in Pharmaceutical Sciences,Remington, 17th Ed., pg. 1104, (1985).

SUMMARY OF THE INVENTION

[0004] In view of the foregoing presentation, it is immediately apparentthat a present and critical need exists for an improvement in thedelivery of hydrocodone for its therapeutic antitussive and analgesiceffects. The need exists for providing a novel therapeutic compositioncomprising hydrocodone, the need exists for providing a novel dosageform comprising hydrocodone, and the need exists for providing a novelmethod for administering hydrocodone to a patient in need of hydrocodonetherapy. It is, therefore, an object of this invention to provide atherapeutic composition comprising hydrocodone with means for enhancingthe administration of hydrocodone over time. It is also an object of theinvention to provide a dosage form with means for controlling thedelivery of hydrocodone that overcomes fluctuation in hydrocodonetherapy. It is an additional object of the invention to provide a methodfor administering hydrocodone for better hydrocodone therapy.

DESCRIPTION OF THE INVENTION

[0005] The drug hydrocodone, as embraced by this invention, comprises amember selected from the group consisting of hydrocodone and itspharmaceutically acceptable salts. Representative of hydrocodonepharmaceutically acceptable salts comprises a member selected from thegroup consisting of hydrocodone bitartrate, hydrocodone bitartratehydrate, hydrocodone hydrochloride, hydrocodone p-toluenesulfonate,hydrocodone phosphate, hydrocodone thiosemicarbazone, hydrocodonesulfate, hydrocodone trifluoroacetate, hydrocodone, hydrocodonebitartrate, dihydrocodeinone bitartrate, hydrocodone bitartratehemipentahydrate, pentafluoropropionate, hydrocodonep-nitrophenylhydrazone, hydrocodone o-methyloxime, hydrocodonesemicarbazone, hydrocodone hydrobromide, hydrocodone mucate, hydrocodoneoleate, hydrocodone phosphate dibasic, hydrocodone phosphate monobasic,hydrocodone inorganic salt, hydrocodone organic salt, hydrocodoneacetate trihydrate, hydrocodone bis(heptafuorobutyrate), hydrocodonebis(methylcarbamate), hydrocodone bis(pentafluoropropionate),hydrocodone bis(pyridine carboxylate), hydrocodonebis(trifluoroacetate), hydrocodone chlorhydrate, and hydrocodone sulfatepentahydrate.

[0006] The following examples are merely illustrative of the invention,and they should not be considered as limiting the scope of the inventionin any way as these examples and other equivalents thereof will becomemore apparent to those versed in the art.

EXAMPLE 1

[0007] A novel, therapeutic composition comprising hydrocodone, whereinthe hydrocodone is a member selected from the group consisting ofhydrocodone pharmaceutically acceptable base and hydrocodonepharmaceutically acceptable salt is prepared as follows: first, 3.00 gof hydrocodone bitartrate hemipentahydrate, 6.45 g of poly(ethyleneoxide) possessing a 200,000 molecular weight and 0.50 g ofhydroxypropylmethylcellulose possessing a 11,200 molecular weight aredry blended on a roll mill at 50% of the maximum speed for 5 minutes.Then, 7 ml of denatured ethyl alchohol and the dry blend are slowlymixed together with a spatula for 5 minutes. After drying, the wettedmass is passed through a 0.03331 inch (0.85 mm) screen, and it is driedovernight at room temperature. Next, 0.049 g of magnesium stearate isblended with the granulation for 2 minutes on a roll mill at 50% ofmaximum speed. Then, a series of extended delivery {fraction (11/32)}inch (8.73 mm) round tablets are prepared by compressing the compositionwith a 1⅛-ton compression force. The high compression force imparts anincrease in density and hardness and a decrease in fluid penetrabilityof the tablet thereby imparting extended delivery to the hydrocodonetablet. This hydrocodone tablet comprises 60 mg of hydrocodonebitartrate hemipentahydrate, 81.75 mg of poly(ethylene oxide), 7.5 mg ofhydroxypropylmethylcellulose, and 0.75 mg of magnesium stearate.

EXAMPLE 2

[0008] The therapeutic composition manufactured by following the aboveexample provides compositions comprising 0.5 mg to 1250 mg of a memberselected from the group consisting of hydrocodone and hydrocodonepharmaceutically acceptable salt; 10 to 350 mg of a polymeric carrierfor the hydrocodone selected from a poly(alkylene oxide) comprising a75,000 to 400,000 molecular weight selected from poly(methylene oxide),poly(ethylene oxide), poly(propylene oxide), poly(isopropylene oxide)and poly(butylene oxide), and 5 to 50 mg of a hydroxyalkylcellulose or ahydroxypropylalkylcellulose possessing a 9,000 to 150,000 molecularweight as represented by a member selected from the group consisting ofhydroxyethylcellulose, hydroxypropylmethylcellulose,hydroxypropylethylcellulose, hydroxypropylisopropylcellulose,hydroxypropylbutylcellulose, and hydroxypropylpentylcellulose; and 0.01to 5 mg of a lubricant selected from the group consisting of magnesiumstearate, calcium stearate, potassium oleate, sodium stearate, stearicacid, sodium palmitate, corn starch, potato starch, bentonite, citruspulp, and stearic acid.

EXAMPLE 3

[0009] Following the procedures of Examples 1 and 2, the hydrocodonecomposition is encapsulated with a semipermeable polymeric compositionprovided with a hydrocodone-releasing orifice to provided an extendeddelivery dosage form.

EXAMPLE 4

[0010] A novel dosage form for delivering hydrocodone substantially freeof delivery fluctuation is prepared as follows: first, 3.00 g ofhydrocodone bitratrate hemipentahydrate, 6.45 g of poly(ethylene oxide)possessing a 200,000 molecular weight, and 0.50 g ofhydroxypropylmethylcellulose possessing a 11,200 molecular weight aredry blended on a roll mill at 50% of the maximum speed for 5 minutes.Then, 7 ml of denatured ethyl alcohol and the dry blend are slowly mixedtogether for 5 minutes. After drying, this wetted mass is passed througha 0.03331 inch (0.85 mm) screen, and then dried overnight at roomtemperature. Next, 0.049 g of magnesium stearate is blended with thegranulation for 2 minutes on a roll mill at 50% of maximum speed. Then,a number of {fraction (11/32)} inch (8.73 mm) tablets are compressedwith 1-ton compression force. Each tablet contains 194 mg of hydrocodonedrug granulation.

[0011] Next, a displacement or push composition comprising 25 to 300 mgof poly(ethylene oxide) of 3,500,000 to 7,500,000 molecular weight, 5 to150 mg of an osmagent, 0 to 30 mg of a hydroxypropylcellulose of 9,200to 175,000 molecular weight, 0 to 10 mg of ferric oxide, 0 to 10 mg oflubricant, and 0 to 3.5 mg of antioxidant is prepared according to theexamples. An embodiment of the displacement or push compositioncomprises 47.76 mg of poly(ethylene oxide) of 7,000,000 molecularweight, 22.5 mg of osmagent sodium chloride, 3.75 mg ofhydroxypropylmethylcellulose of 11,200 molecular weight, 0.18 mg offerric oxide, 0.75 mg of magnesium stearate, and 0.06 mg of butytlatedhydroxytolune is prepared by the accompanying procedure.

[0012] The push granulation is fluid bed granulated at 120 kg scale on afluid bed granulator. A binder solution is made by dissolvinghydroxypropylmethylcellulose, butylated hydroxytoluene in water andethanol. This binder solution is sprayed onto the poly(ethylene oxide),sodium chloride, hydroxypropylmethylcellulose and ferric oxide blend,while the blend is fluidized and is forming granules. After thegranulation is dried, the granulation is milled in a fluid air mill.Next, a lubricant magnesium stearate is added to the dry granulation.

[0013] A semipermeable composition comprising 80:19:1, wt:wt:wt, mixtureof cellulose acetate comprising an acetyl content of 39.8%,poly(vinylpyrrolidone) and triethylcitrate dissolved in an 80:20, v:v,mixture of acetone and methanol at 4% solids is sprayed around thebilayer core comprising a compressed layer of hydrocodone compositionand a compressed layer of push composition to provide a compressedbilayer, to apply the semipermeable wall. Next, a 25 mil (0.64 mm)orifice is drilled into each dosage form and the dosage form driedovernight at 40° celsius. The semipermeable wall weighed 35 mg. Thedosage form has a mean release rate of 6.44 mg/hr over 15 hours.

EXAMPLE 5

[0014] Following the above procedure, dosage forms are providedpossessing a hydrocodone rate of release of 0.5 mg to 10 mg per hourover 20 hours.

EXAMPLE 6

[0015] The osmagent for the purpose of this invention in the hydrocodoneand push compositions comprises a member selected from the osmoticsolutes consisting of magnesium sulfate, sodium chloride, lithiumchloride, potassium sulfate, sodium sulfate, lithium sulfate, potassiumacid phosphate, mannitol, urea, inositol, magnesium succinate, tartaricacid, carbohydrates like raffinose, sucrose, glucose, lactose, fructose,sodium chloride, and fructose, and potassium chloride and dextrose.

EXAMPLE 7

[0016] The procedures above described are followed for the controlleddelivery of hydrocodone at a metered rate is prepared wherein the dosageform comprises a hydrocodone layer comprising 58.08 mg of hydrocodonebitartrate hemipentahydrate, 125.06 mg of poly(ethylene oxide)possessing a 200,000 molecular weight, 9.8 mg ofhydroxypropylmethylcellulose of 9,400 molecular weight, and 0.97 mg ofmagnesium stearate. A push layer comprising 47.76 mg of poly(ethyleneoxide) possessing a 7,000,000 molecular weight, 22.5 mg of osmoticsolute sodium chloride, 3.75 mg of hydroxypropylmethylcellulose of11,200 molecular weight, 0.75 mg of magnesium stearate, 0.18 mg offerric oxide and 0.06 mg of butylated hydroxytoluene. The bilayercompositions are surrounded by a semipermeable wall comprising 25.92 mgof cellulose acetate comprising 39.8% acetyl content, 6.15 mg ofpoly(vinylpyrrolidone) of 40,000 molecular weight and 0.324 mg ofplasticizer triethyl citrate. The dosage forms comprise a 25 mil (0.64mm) orifice and exhibits a mean release rate of 5.105 mg/hr ofhydrocodone over a sustained period of therapy over 16 hours.

EXAMPLE 8

[0017] The procedures of the above examples are followed to produce ahydrocodone composition comprising 60.00 mg of hydrocodone bitartratehemipentahydrate, 81.75 mg of poly(ethylene oxide) of 200,000 molecularweight, 7.50 mg of hydroxypropylmethylcellulose of 9,200 molecularweight, and 0.75 mg of magnesium stearate. The semipermeable wall thatsurrounded the hydrocodone comprises 75:24:1, wt:wt:wt, mixture ofcellulose acetate with an acetyl content of 39.8%,poly(vinylpyrrolidone) of 40,000 molecular weight and triethyl citrate.The semipermeable composition is dissolved in a 80:20, v:v, mixture ofacetone and methanol at 4% solids. The semipermeable wall weighed 43.4mg.

EXAMPLE 9

[0018] Representative of antioxidants for providing the dosage forms ofthis invention comprise a member selected from the group consisting ofd-alpha tocopherol, dl-alpha tocopherol, d-alpha-tocopherol acetate,dl-alpha-tocopherol, ascorbyl palmitate, ascorbic acid, butylatedhydroxyanisole, butylated hydroxytoluene, and propyl gallate.

EXAMPLES 10-11

[0019] The procedure of the above examples is followed except in theseexamples there is provided in one manufacture a hydrocodone compositioncomprising a poly(ethylene oxide) consisting of a 100,000 molecularweight, and in another manufacture the hydrocodone composition comprisesthe hydrocodone composition comprising a poly(ethylene oxide) of 300,000molecular weight.

EXAMPLE 12

[0020] The wall provided by the above examples are semipermeablepossessing a permeability to aqueous including biological fluids andimpermeable to hydrocodone. The semipermeable walls comprise 15 mg to200 mg of a cellulose polymer selected from the group consisting of acellulose ester, cellulose diester, cellulose triester, cellulose ether,cellulose ester-ether, cellulose acylate, cellulose diacylate, cellulosetriacylate, cellulose acetate, cellulose diacetate, and cellulosetriacetate; the wall comprises 0 to 5 mg of a plasticizer represented bya member selected from the group consisting of trimethyl citrate,triethyl citrate, tributyl citrate, acetyltributyl citrate, acetyltri-2-ethyl citrate, tributyl phosphate, triethyl phosphate, triphenylcitrate, tricyclohexyl citrate, and tricresyl citrate; the semipermeablewall comprises 2 mg to 50 mg of a poly(vinyl) polymer possessing a10,000 to 200,000 molecular weight as represented by poly(vinylpyrrolidone), copolymer of poly(vinyl-pyrrolidone and (vinyl acetate),copolymer of poly(vinyl pyrrolidone and vinyl alcohol), copolymer ofpoly(vinyl pyrrolidone and vinyl chloride), copolymer of poly(vinylpyrrolidone and vinyl fluoride), copolymer of poly(vinyl pyrrolidone andvinyl butyrate), copolymer of poly(vinyl pyrrolidone and vinyllaurate),and copolymer of poly (vinyl pyrrolidone and vinyl stearate).

[0021] Exemplary solvents used for the present purpose compriseinorganic and organic solvents that do not adversely harm the materialsand the final wall or the final compositions in the dosage form. Thesolvents broadly include members selected from the group consisting ofaqueous solvents, alcohols, ketones, esters, ethers, aliphatichydrocarbons, halogenated solvents, cycloaliphatics, aromatics,heterocyclic solvents, and mixtures thereof. Typical solvents includeacetone, diacetone alcohol, methanol, ethanol, butyl alcohol, methylacetate, ethyl acetate, isopropyl acetate, n-butyl acetate, methylisobutyl ketone, methyl propyl ketone, n-hexane, n-heptane, ethyleneglycol monoethyl ether, ethylene glycol monethyl acetate, methylenedichloride, ethylene dichloride, propylene dichloride, carbontetrachloride, chloroform, nitroethane, nitropropane, tetrachloroethane,ethyl ether, isopropyl ether, cyclo-hexane, cyclo-octane, benzene,toluene, naphtha, 1,4-dioxane, tetrahydrofuran, diglyme, aqueous andnonaqueous mixtures thereof, such as acetone and water, acetone andmethanol, acetone and ethyl alcohol, methylene dichloride and methanol,and ethylene dichloride and methanol.

[0022] Exit means, as used in the above examples for the dosage forms asused by this invention comprise means and methods suitable for themetered release of beneficial drug hydrocodone from the dosage form. Theexit means comprises at least one passageway, orifice, or the like,through the wall for communicating with hydrocodone the dosage form. Theexpression, “at least one passageway,” comprises aperture, orifice,bore, pore, porous element through which the hydrocodone can migrate,hollow fiber, capillary tube, porous overlay, porous insert, and thelike. The expression also includes a material that erodes or is leachedfrom the wall in the fluid environment of use to produce least onepassageway in the dosage form. Representative materials suitable forforming at least one passageway, or a multiplicity of passageways,include an erodible poly(glycolic) acid, or poly(lactic) acid member inthe wall, a gelatinous filament, poly(vinyl alcohol), leachablematerials such as fluid removable pore forming polysaccharides, salts,oxides, or the like. A passageway or a plurality of passageways can beformed by leaching a material such as sorbitol, lactose, fructose andthe like from the wall. The passageway can have any shape such as round,triangular, square, elliptical, and the like, for assisting in themetered release of hydrocodone from the dosage form. The dosage form canbe constructed with one or more passageways in spaced apart relations,or more than one passageway on a single surface of a dosage form.Passageways and equipment for forming passageways are disclosed in U.S.Pat. Nos. 3,845,770, 3,916,899; 4,063,064; and 4,088,864. Passageways ofgovern size formed by leaching are disclosed in U.S. Pat. Nos. 4,200,098and 4,285,987.

EXAMPLE 13

[0023] A dosage form adapted, designed and shaped for the oral deliveryof hydrocodone to a patient in need of hydrocodone therapy ismanufactured as follows: first, 8.00 g of hydrocodone bitartratehemipentahydrate, 5.50 g of sorbitol, 4.20 g of sodiumcarboxymethylcellulose possessing a 90,000 molecular weight and 1.00 gof hydroxypropylmethylcellulose of 9,200 molecular weight are screenedseparately through a 0.0165 inch (0.42 mm) 40 mesh screen. Next, thescreened materials are blended on a three roll mill for 20 minutes toproduce a homogenous blend. Then, a granulation is prepared bydissolving 1.20 g of poly(vinyl pyrrolidone) having a 40,000 molecularweight and 10 ml of denatured ethyl alcohol with constant stirring toprovide a granulation fluid. Then, to all the ingredients on the millingmachine, the granulation fluid is slowly added, and all the ingredientsblended slowly for 5 minutes, to yield a wet granulation. The wettedmass is then passed through a 0.03331 inch (0.85 mm) 20 mesh screen andair dried at room temperature in a light current of moving air. Afterdrying, the granulation is blended for an additional 2 minutes on astandard roll mill at 50% of its maximum speed. Then, {fraction (5/16)}inch (7.94 mm) round tablets, each comprising 150 mg of the hydrocodonecomposition are compressed on a Carver® press under a ¼-ton compressionforce to provide the first layer of a bilayer core. The hydrocodonecomposition comprises 60.00 mg of hydrocodone bitartratehemipentahydrate, 41.25 mg of sorbitol, 31.50 mg of sodiumcarboxymethylcellulose possessing a 90,000 molecular weight 9.00 mg ofpoly(vinylpyrrolidone) possessing a 40,000 molecular weight, 7.50 mg ofhydroxypropylmethylcellulose possessing a 9,200 molecular weight and0.75 mg of magnesium stearate.

[0024] A composition for providing a push layer of a bilayer corearrangement is prepared comprising 44.06 mg of sodiumcarboxymethylcellulose possessing a 700,000 molecular weight, 22.50 mgof sodium chloride, 3.75 mg of hydroxypropylmethylcellulose possessing a11,200 molecular weight, 0.75 mg of ferric oxide and 0.19 mg ofmagnesium stearate are used for preparing the push composition. A pushgranulation is prepared on a fluid bed granulator. A binder solution ismade by dissolving hydroxypropylmethylcellulose in water. The bindersolution is sprayed on the sodium carboxymethylcellulose 7H possessing a700,000 molecular weight, the sodium chloride,hydroxypropylmethylcellulose and ferric oxide push-forming blend whilethe blend is fluidized and the granules are formed in the granulator.After the granulation is dried overnight at room temperature, the blendis remilled in a fluid air mill, and magnesium stearate is added to themill.

[0025] The push-forming coposition is compressed into a {fraction(5/16)} inch (7.94 mm) round layer with each layer comprising 75 mg ofthe push composition using a Carver® press under a compression force of1⅛-ton to provide the second layer of the bilayer core. The hydrocodonelayer and the push layer are coated with a semipermeable wall-formingcomposition in a 12 inch (30 cm) coater. The semipermeable wall-formingcomposition comprises a 75:24:1, wt:wt:wt, mixture of cellulose acetatehaving a 39.8% acetyl content, poly(vinylpyrrolidone) having a 40,000molecular weight, and triethyl citrate. The wall-forming components aredissolved in a 80:20, wt:wt, mixture of acetone and methanol at 4%solids. The average wet semipermeable wall weighted 36.8 mg. A single 25mil (0.64 mm) passageway is drilled into each dosage form, and then thedosage forms are dried overnight at 40° celsius. The dosage formexhibited a mean release rate of 8.212 mg/hr over an extended 12 hoursof therapy.

EXAMPLE 14

[0026] The procedure of the above example is followed for manufacturinga dosage form, characterized by a hydrocodone layer consisting of 0.5 to1250 mg of hydrocodone, 10 to 50 mg of sorbitol, 10 to 50 mg of alkalicarboxymethylcellulose of 70,000 to 400,000 molecular weight, 5 to 50 mgof hydroxypropylalkylcellulose of 9,000 to 150,000 molecular weight, 0to 20 mg of poly(vinyl-pyrrolidone) of 10,000 to 140,000 molecularweight, and 0.01 to 5 mg of a lubricant; and a push compositioncomprising 10 to 60 mg of alkali carboxymethylcellulose of 650,000 to1,200,000 molecular weight, which is a higher molecular weight then themolecular weight of the alkali carboxymethylcellulose present in thehydrocodone composition, 5 to 75 mg of osmagent, 1 to 30 mg ofhydroxypropylmethylcellulose, 0 to 10 mg of ferric oxide, and 0 to 10 mgof lubricant.

DISCLOSURE FOR USING THE INVENTION

[0027] The invention concerns also a method for administering 0.5 mg to1250 mg of hydrocodone to a patient in need of hydrocodone therapy. Themethod, in one administration comprises admitting orally into thepatient 0.5 mg to 1250 mg of a hydrocodone selected from the groupconsisting of hydrocodone, and hydrocodone pharmaceutically acceptablesalt, which is administered from a therapeutic composition comprising0.5 mg to 1250 mg of hydrocodone, 10 mg to 350 mg of a poly(alkyleneoxide) of 75,000 to 400,000 molecular weight, 5 mg to 50 mg of ahydroxyalkylcellulose of 9,000 to 150,000 molecular weight and 0.01 mgto 5 mg of a lubricant, which composition provides hydrocodone therapyover an extended period of time.

[0028] The invention concerns further a method for administering 0.5 mgto 1250 mg of hydrocodone by admitting orally 0.5 mg to 1250 mg ofhydrocodone to a patient administered from a dosage form comprising asemipermeable wall permeable to aqueous and biological fluid andimpermeable to the passage of hydrocodone, which semipermeable wallsurrounds an internal compartment comprises a hydrocodone compositionand a push composition. The hydrocodone composition consists of thecomposition above, and the push composition comprises 25 to 300 mg of apoly(alkylene oxide) of 3,000,000 to 7,500,000 molecular weight, 5 mg to150 mg of an osmagent, 1 to 30 mg of a hydroxypropylmethylcellulose of9,200 to 175,000 molecular weight, 0 to 10 mg of ferric oxide, 0 to 10mg of lubricant and 0 to 3.5 mg of an antioxidant; and an exit means inthe semipermeable wall for delivering the hydrocodone from the dosageform. The dosage form delivers the hydrocodone by imbibing fluid throughthe semipermeable wall into the dosage form causing the hydrocodonecomposition to change from a resting state to a dispensable state, andsimultaneously causing the push composition to imbibe fluid, expand andpush the hydrocodone composition through the exit, whereby through thecombined operations of the dosage form the hydrocodone is delivered at atherapeutically effective dose at a controlled over an extended periodof time.

[0029] Inasmuch as the foregoing specification comprises numerousembodiments, it is understood that variations and modifications can bemade herein, in accordance with the principles disclosed, withoutdeparting from the invention.

1. A therapeutic composition comprising 0.5 to 1250 mg of hydrocodone,10 mg to 350 mg of a poly(alkylene oxide) possessing a 75,000 to 400,000molecular weight, 5 mg to 50 of hydroxyalkylcellulose possessing a 9,000to 150,000 molecular weight, and 0.01 mg to 5 mg of a lubricant.
 2. Thetherapeutic composition according to claim 1, wherein the hydrocodone isselected from the group consisting of hydrocodone pharmaceuticallyacceptable salt, hydrocodone bitartrate hemipentahydrate, hydrocodonebitartrate, hydrocodone bitartrate hydrate, hydrocodone hydrochloride,hydrocodone phosphate, hydrocodone sulfate, hydrocodone mucate,hydrocodone sulfate pentahydrate and hydrocodone oleate.
 3. Thetherapeutic composition according to claim 1, wherein the composition iscompressed under 1⅛ to 10-ton force compression, and a semipermeablewall with an exit passageway encased the therapeutic composition.
 4. Atherapeutic composition comprising 0.5 to 1250 mg of hydrocodone, 10 to50 mg of alkali carboxymethylcellulose of 70,000 to 400,000 molecularweight, 5 to 50 mg of hydroxypropylalkylcellulose of 9,000 to 150,000molecular weight, and 0.01 to 5 mg of a lubricant.
 5. The therapeuticcomposition according to claim 4, wherein the therapeutic compositioncomprises poly(vinylpyrrolidone).
 6. The therapeutic compositionaccording to claim 4, wherein the therapeutic composition comprisessorbitol.
 7. The therapeutic composition according to claim 4, whereinthe hydrocodone is selected from the group consisting of hydrocodonebitartrate hemipentahydrate, hydrocodone bitartrate, hydrocodonehydrochloride, hydrocodone phosphate and hydrocodone sulfate.
 8. Thetherapeutic composition according to claim 4, wherein a semipermeablewall with an exit passageway surrounds the therapeutic composition.
 9. Abilayer composition comprising a hydrocodone layer comprising 0.5 to1250 mg of hydrocodone, 10 mg to 350 mg of a poly(alkylene oxide) of75,000 to 400,000 molecular weight, 5 to 50 mg of ahydroxyalkylcellulose of 9,000 to 450,000 molecular weight and 0.01 to 5mg of a lubricant; and a push layer comprising 25 to 300 mg of apoly(alkylene oxide) of 3,000,000 to 7,500,000 molecular weight, 5 to150 mg of an osmagent, and 1 to 30 mg of a hydroxypropylalkylcelluloseof 9,200 to 175,000 molecular weight.
 10. The bilayer compositionaccording to claim 4, wherein the push composition comprises anantioxidant.
 11. The bilayer composition according to claim 4, whereinthe push composition comprises a lubricant.
 12. The bilayer compositionaccording to claim 4, wherein a semipermeable wall with an exitpassageway surrounds the bilayer composition.
 13. A bilayer compositioncomprising a hydrocodone layer comprising 0.5 to 1250 mg of hydrocodone,10 to 50 mg of alkli carboxymethylcellulose comprising a 70,000 to400,000 molecular weight, 5 to 50 mg of hydroxypropylalkylcellulose of9,000 to 150,000 molecular weight; and a push layer comprising 10 to 60mg of an alkali carboxymethylcellulose of 650,000 to 1,200,000 molecularweight, 5 to 75 mg of an osmagent, and 1 to 30 mg of ahydroxypropylalkylcellulose of 9,000 to 150,000 molecular weight. 14.The bilayer composition according to claim 13 wherein the hydrocodonelayer comprises a poly(vinylpyrrolidone).
 15. The bilayer compositionaccording to claim 13, wherein a semipermeable wall comprising apassageway surrounds the bilayer composition.
 16. A method foradministering 0.5 to 1250 mg of hydrocodone to a patient in need ofhydrocodone therapy, which method comprises admitting orally into thegastrointestinal tract of the patient a sustained delivery compositioncomprising the hydrocodone, and a polymer carrier for the hydrocodonecomprising a 75,000 to 400,000 molecular weight that is delivered at arate of release of 0.5 mg to 10 mg per hour over a sustained period of20 hours.
 17. The method for administering the hydrocodone according toclaim 16, wherein the hydrocodone composition is surrounded by asemipermeable wall permeable to the passage fluid in thegastrointestinal tract and impermeable to the passage of hydrocodone,with a passageway in the semipermeable wall for delivering thehydrocodone to the patient.
 18. A method for administering 0.5 to 1250mg of hydrocodone to a patient in need of hydrocodone therapy, whichmethod comprises orally administering the hydrocodone at a rate of 0.5mg to 10 mg per hour over 20 hours, for hydrocodone therapy.
 19. Amethod for administering 0.5 to 1250 mg of hydrocodone to a patient inneed of hydrocodone therapy, which method comprises orally admittinginto the gastrointestinal tract of the patient a bilayer comprising ahydrocodone layer comprising 0.5 to 1250 mg of hydrocodone, 10 mg to 350mg of poly(alkylene oxide) possessing a 75,000 to 400,000 molecularweight, 5 to 50 mg of a hydroxyalkylcellulose of 9,000 to 450,000molecular weight and 0.01 to 5 mg of a lubricant; and a push layercomprising 25 mg to 300 mg of a poly(alkylene oxide) of 3,000 to7,500,000 molecular weight 5 to 150 mg an osmagent, and 1 to 30 mg of ahydroxypropylalkylcellulose of 9,200 to 175,000 molecular weight, whichbilayer delivers the hydrocodone over a period of 30 hours to thegastrointestinal tract of the patient.